The rapid development of lifescience and medicine has increased the average life expectancy of humans, and a gradual increase in the number of the aging population is creating new social problems. Particularly, age-related neurodegenerative diseases including strokes, Alzheimer's disease (AD) and Parkinson's disease (PD), can appear as fatal nervous dysfunctions. Under current circumstances, there is no effective method capable of preventing these diseases, and thus these diseases reduce quality of life, cause a large amount of medical expenses, and impose a significant burden on the patient's family. Due to the severity of such problems, efforts to overcome these diseases have been made worldwide. For example, the United States announced the Decade of the Brain on Jan. 1, 1990, and Japan has announced the Century of the Brain. In addition, South Korea established Braintech 21 in 1998.
Alzheimer's disease develops in 2% of elderly who are 60 years old, and medical technology is spreading to underdeveloped countries. However, due to an increase in the aging population, about 20,030,000 Alzheimer's patients in the year 2025 are expected to exist (http://www.alz.co.uk/). In the case of stroke, it is estimated that about 15,000,000 will occur in the year 2025. In the USA, in the year 1997, 4,000,000 AD patients and 3,000,000 stoke patients were diagnosed and incurred about $1,300. Based on this, it is estimated that medical expenses caused by the above two diseases are about $4,000 (520 trillion won) in the year 2003. In Korea, brain diseases occurring in old people are major causes of death and will place financial strain on the development of the national economy and the national health service.
Alzheimer's disease (hereinafter referred to as AD) is a brain nerve disease that is the most common form of dementia, and accounts for 70% of dementia cases and results in the loss of cognitive ability due to the progressive degeneration of nerve cells. In AD, brain portions that are involved in attention, memory and language functions are damaged, so that memory is lost, consciousness becomes unclear, and cerebral functions, including thinking, calculation, discernment and common sense are impaired, making occupational and social activities difficult.
The brain of patients who die of AD is pathologically characterized by senile plaques and neurofibrillary tangles. The senile plaques are formed by the extracellular accumulations of proteins and dead cells, and the major component thereof is β-amyloid peptide. Also, the major component of the neurofibrillary tangles is tau protein. The tau protein functions as a structure that strengthens nerve cells in the central nervous system. However, in the brain of dementia patients, this tau protein is chemically altered to form tangles. For this reason the tau protein disrupts communication between nerve cells, resulting in nerve cell death.
Studies associated with AD to date resulted in the development of preventive and therapeutic agents for AD mainly using agents inhibiting beta-amyloid production and inhibitors of neurotoxicity, such as antioxidants. Current medications for AD include nicotinic receptor agonists, such as ABT-418; muscarinic receptor agonists, such as Xanomeline and YM-976; acetylcholine precursors, such as lecithin and acetyl-L-carnitine; metal chelators, such as desferrioxamine and lioquinol; beta-sheet breakers, such as iAβ5 and iAβ11; antioxidants, such as vitamin E, Ginkgo biloba, melatonin and idebenone; sAPP releasing agents, such as nicotine, acetylcholine and carbachol; β-secretase or γ-secretase inhibitors, such as OM99-1, OM99-2, OM99-3 and Z-VLL-CHO; non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and indomethacin; hormones such as estrogen; vaccines, such as AN-1792; and cholesterol-lowering agents, such as simvastatin and atorvastatin. However, most medications are only marginally helpful in slightly relieving the pathological symptoms of AD or slowing AD progression, or are difficult to apply in practice due to their toxicity. Thus, there remains an urgent need for the development of stable and effective drugs for AD treatment. Recent AD-associated studies have been focused on the identification of the neurotoxic mechanisms of beta-amyloid. Pro-apoptotic genes, such as prostate apoptosis response-4 (Par-4), tau protein kinase 1 (GSK-3β), Calsenilin/DREAM/KChIP3, and cell death-promoting gene 5 (DP5), are shown to be overexpressed or their activities are increased in neuronal cells cultured in the presence of beta-amyloid or neuronal cells from AD patients. The blocking of the functions of the proteins reduces beta-amyloid-induced neuronal death. However, these reports are not sufficient to identify an intracellular signaling pathway for beta-amyloid-induced neuronal toxicity so as to develop AD drugs for preventing beta-amyloid-induced neuronal loss.
Meanwhile, Korean Patent Laid-Open Publication No. 99-85202 discloses a ginseng-based product obtained by mixing several kinds of herbs and extracting the mixture. However, because this product is based on a ginseng component, it can cause adverse effects such as palpitations or homeostasis imbalance in hypertension patients. Thus, in the case of conventional compositions for dementia treatment, the adverse effects thereof become the biggest problem, and particularly, herbal medicinal preparations have significantly less adverse effects compared to other medications, but can cause other adverse effects in some cases. Thus, there is an urgent need for the development of a composition which causes no adverse effects.
The present inventors have made extensive efforts to find plants and extracts thereof having no adverse effects and, as a result, have paid attention to black beans. Anthocyanin contained in black beans is a common substance in higher plants and cause colors to be shown in flowers and fruits and also belongs to the family of flavonoids which are pigments found in plant vacuoles. Anthocyanin appears red, purple or green depending on the pH of plants. It is known to protect plant cells from UV rays and insect invasion. Free oxygen radicals are generated by a process in which food is metabolized in the human body. The generated free oxygen radicals react with cell molecules in vivo to oxidize cells. As is well known in the art, when cells are oxidized, the cells are broken down to cause various diseases or to cause cancer by DNA denaturation. Antioxidants bind to free oxygen radicals to prevent cell oxidation and have antioxidant activity.
Known antioxidants include vitamin C, vitamin E, beta-carotene and the like, and in recent years, anthocyanin has received attention as a potent antioxidant in the medical world. Plants known to have anthocyanin include purple carrots, cranberries, blueberries and the like, but the effects of anthocyanin on the improvement of memory and the amelioration of dementia have not yet been known.
Accordingly, the present inventors have made extensive efforts to find a substance effective in improving memory and ameliorating dementia without side effects and, as a result, have found that an anthocyanin component extracted from black beans inhibits and reduces the accumulation of BACE-1 enzyme which is involved in the formation of β-amyloid protein found in the brain of rats having Alzheimer's disease induced by administration of β-amyloid, suggesting that it is effective in treating or ameliorating neurodegenerative brain diseases, thereby completing the present invention.